Invariant natural killer T (iNKT) cells are important in both innate and the adaptive immunity. Once activated, they release massive amounts of inflammatory cytokines and play an important pro-inflammatory role in a range of disease processes, including autoimmune diseases, infectious diseases, and cancer. Commensal microbiota can modulate iNKT cell numbers in vivo, including in the gut and in the lungs. As a result, conventionally colonized mice (e.g., the normal mouse microbiome) have significantly fewer iNKT cells in these two compartments compared to germ-free mice. When challenged in iNKT cell-dependent asthma and ulcerative colitis models, the conventional mice are protected while the germ-free mice had severe disease phenotypes, suggesting that low numbers of iNKT cells in the colon and lung are associated with resistance to experimental colitis and asthma.